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The connection Between Plasma Protein Binding and Acute Toxicity as Determined by the LD 50 Value
Author(s) -
Svennebring Andreas
Publication year - 2016
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21286
Subject(s) - lipophilicity , toxicity , acute toxicity , therapeutic index , chemistry , pharmacology , plasma concentration , blood proteins , drug , biochemistry , medicine , organic chemistry
Preclinical ResearchA dataset of three drug classes (acids, bases, and neutrals) with LD 50 values in mice was analysed to investigate a possible connection between high plasma protein binding and acute toxicity. Initially, it was found that high plasma protein binding was associated with toxicity for acids and neutrals, but after compensating for differences in lipophilicity, plasma protein binding was found not to be associated with toxicity. The therapeutic index established by the quotient between mouse LD 50 and the defined daily dose was unaffected by both lipophilicity and plasma protein binding. Drug Dev Res 77 : 3–11, 2016. © 2015 Wiley Periodicals, Inc.